Bacteria first species observed to use arsenic-laced DNA backbone

Phosphorus is fundamental to the chemistry of DNA, but a bacterial strain has …

All living organisms on this planet use six elements for almost all of the chemical structures of DNA, RNA, proteins, and lipids. There is a smattering of other elements, mostly metals, that are essential for biological functions (e.g., the iron in hemoglobin). However, we wouldn’t expect to find anything outside of carbon, hydrogen, oxygen, nitrogen, sulfur and phosphorus in the basic structures of biomolecules. Surprisingly, a team of scientists provide evidence in Science that another element, arsenic, can be incorporated into the basic chemical makeup of the macromolecules of life, replacing some of its phosphorus.

Evolutionary geochemist Felisa Wolfe-Simon, the lead author, and her colleagues found a strain of bacterium (GFAJ-1 of the Halomonadaceae family) that can grow in a medium abundant in arsenic and lacking phosphorus. The GFAJ-1 bacterium naturally resides in the arsenic-rich waters (200 uM) of Mono Lake located in California's Eastern Sierra, and it belongs to a family of proteobacteria that is known to accumulate arsenic. It's not remarkable that GFAJ-1 survives in high concentrations of arsenic, but what is startling is that it potentially integrates arsenic into its DNA and proteins.

Arsenic is chemically similar to phosphorus, which has a large presence in biomolecules in the form of phosphate (PO43-). That’s partly why arsenic is so toxic. In physiological conditions, phosphate and arsenate (AsO43-) are analogous enough that some metabolic pathways cannot tell them apart initially. But incorporation of arsenic disrupts later steps in these pathways, most likely due to arsenic compounds’ relative instability and lower resistance to hydrolysis.

The researchers propose that, if an organism possesses an ability to overcome arsenate’s instability, it might be able to exchange phosphorus for arsenic in biological pathways. To test their hypothesis, they extracted GFAJ-1 from Mono Lake and subjected the bacteria to an artificial medium with increasing concentrations of arsenate and only trace amounts of phosphate.

GFAJ-1 bacteria grew slower with arsenate than they would with phosphate, but they were still able to increase their cell count by 20-fold in six days. The cells ended up containing 0.19 percent arsenic by dry weight compared to just 0.001 percent in the control cells. More importantly, the cells grown in arsenate were noticeably different in morphology from the control population. They were 1.5 times bigger by volume and developed large vacuole-like regions inside the cells.

Rather than just retaining arsenic inside the cells, the authors provided evidence that the bacteria actually integrated arsenic into DNA and possibly other biomolecules. They found higher arsenic and lower phosphorus content in purified genomic DNA of bacteria grown in arsenate compared to control cells.

Synchrotron X-ray studies of intracellular arsenic revealed that it is mostly likely bound to four oxygen atoms and then distally bound to a carbon atom. This configuration is consistent with arsenic replacing phosphorus in the backbone DNA. Substitution of elements is known to occur in biological processes (e.g., copper in hemocyanin vs. iron in hemoglobin for oxygen transport), but it has not been seen in something as fundamental as the structure of DNA, nor has it been observed with arsenic.

The researchers found evidence that bacteria may also incorporate arsenic into proteins and metabolites. Fractions from cellular extractions corresponding to proteins and metabolites contained significant amounts of arsenic, suggesting that it is chemically integrated. Nonetheless, high resolution analysis of purified products would provide more concrete evidence.

Somehow GFAJ-1 found a way to compensate for the instability of arsenate and use it to alter the chemical makeup of its primary biomolecules. The authors propose that the vacuole-like regions could contain large amounts of poly-β-hydroxybutyrate, which stabilizes arsenic compounds and could assist the assimilation of arsenate.

The researchers’ discovery that bacteria can substitute phosphorus with arsenic in the backbone of DNA has significant implications for evolutionary chemistry and astrobiology, since it suggests that life won't necessarily be limited to the six elements it favors here on Earth. In fact, NASA announced a press conference on these results as relevant to the search for extraterrestrial life, which set off a wave of speculation as to what the agency knew.

Further investigation is necessary to find the exact mechanism of arsenic substitution. Moreover, these research results raise the question of whether or not other elements can stand-in for one of life’s six key elements.

Really interesting stuff. It's amazing how nature finds a way to adapt life to very different circumstances.

I would recommend the book "A Guided Tour of the Living Cell" by Christian de Duve for a great background on the structure of cells and the biochemistry behind DNA and protein manufacture. The books are easy to get into, but also go quite deep into some of the chemistry.

Like other groups, the members of this family show patterns in its electron configuration, especially the outermost shells resulting in trends in chemical behavior.

Outer shell confirmation dictates how an atom plays with others. The silicon-based life form concept is not too far off since Carbon and Silicon are related by the same manner. Biochemistry and the rationales for either choice of similar outer shell atoms interchangeability not included.

I thought this was an exceptionally good article so I just wanted to say thanks.

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Very well written. I was able to grasp the implications of the science (extra-terrestrial life could exist in systems without the key six elements) with just my educational foundation consisting of high school bio and 100 level college chem.

Molecular biologist Steven Benner, who is part of NASA's "Team Titan" and an expert on astrobiology, gave an interview to Fox news. There is this, seemingly ridiculous quote: "In his estimation, we've always defined life as something that has the exact same chemistry as a life-form on Earth. The new discovery will likely change that equation, because it means the basic building blocks of DNA are not quite what we thought." And then later, this: ""It's a paradigm shift," says Dimitar Sasselov, an astrobiologist who leads the Origins of Life Initiative at Harvard University. "The possibility that Earth-life biochemistry is not universal is a transformational concept."

This kills me. The possibility that Earth-life biochemistry is not universal is the foundation of almost everything ever I've ever read in science fiction and speculative science regarding extraterrestrial life. Maybe it's surprised these yahoos. I never expected life on other planets to be exactly the same. I'd have been astonished if it hadn't been different.

This kills me. The possibility that Earth-life biochemistry is not universal is the foundation of almost everything ever I've ever read in science fiction and speculative science regarding extraterrestrial life. Maybe it's surprised these yahoos. I never expected life on other planets to be exactly the same. I'd have been astonished if it hadn't been different.

One of the great things about Fiction is that you don't need any evidence to build a story from an idea. "What if..." is the fundamental component of all good fiction, especially Science Fiction.

The difference between Fiction and Science, though, is that you need evidence of some difference before you can change a theory. Until this was found procedurally and defined scientifically, there was only *speculation* that life could form around other elements; all of the evidence to this point (meaning "life as we know it") had indicated that life used six elements for the chemical structures of DNA, RNA, proteins, and lipids.

The difference between Fiction and Science, though, is that you need evidence of some difference before you can change a theory. Until this was found procedurally and defined scientifically, there was only *speculation* that life could form around other elements; all of the evidence to this point (meaning "life as we know it") had indicated that life used six elements for the chemical structures of DNA, RNA, proteins, and lipids.

It's really nice to see these kinds of informed comments in the Ars community. A number of people I've talked to about this seem to either be in the "ZOMG NASA found aliens in California!" camp, or the "How is this new? People have been talking about alternate life forms for /ages/" camp.

This kills me. The possibility that Earth-life biochemistry is not universal is the foundation of almost everything ever I've ever read in science fiction and speculative science regarding extraterrestrial life. Maybe it's surprised these yahoos. I never expected life on other planets to be exactly the same. I'd have been astonished if it hadn't been different.

One of the great things about Fiction is that you don't need any evidence to build a story from an idea. "What if..." is the fundamental component of all good fiction, especially Science Fiction.

The difference between Fiction and Science, though, is that you need evidence of some difference before you can change a theory. Until this was found procedurally and defined scientifically, there was only *speculation* that life could form around other elements; all of the evidence to this point (meaning "life as we know it") had indicated that life used six elements for the chemical structures of DNA, RNA, proteins, and lipids.

Just to add to what you were saying, I thought it would also be important to note that scientists have also discovered life-forms that are able to survive in harsh climates heat-wise and radiation-wise, as well as types of bacteria that can potentially live without water, substituting liquid methane for biological functions.

Coupling all these things together just adds more to the likelihood of extraterrestrial life.

If this is related to the NASA press conference, then can someone explain to me what all the hubub is about? I mean, here we have a bacteria -- an already developed and accepted form of life -- that was essentially trained to replace one low-availability element that's critical to it's biological processes with another one that happened to have been readily available. Isn't this just adaptation to an extreme environment -- with some pretty heavy-handed external input (in the form of a researcher forcing the environment to get even more extreme) even?

This is neat and all in my semi-educated and not-so-humble opinion, but not "startling implications for the search for extra-terrestrial life" big. It'd be different if this were shown to have developed on it's own without input from "normal" biological life, but as it is it looks like just another extremophile to me.

This is huge and opens up a lot of possibilities. There's a pretty decent wikipedia article on hypothetical alternate biochemistries. Looks like someone already updated the Arsenic section to reflect this new discovery. It makes you wonder if any of these other biochemistries will prove valid.

This is neat and all in my semi-educated and not-so-humble opinion, but not "startling implications for the search for extra-terrestrial life" big. It'd be different if this were shown to have developed on it's own without input from "normal" biological life, but as it is it looks like just another extremophile to me.

The big deal is that it's not just tolerant of arsenic, it's that it actually integrates it into its bio-molecules. No other life form's ever been known to do so, and if this one exists, chances are there are others out there. The implication for extra-terrestrial life searches is that we can't just rely on looking only for the signatures of the 6 chemical elements that we previously thought all life had to be composed of, as this validates the possibility that completely different biochemistries are in fact viable.

This is neat and all in my semi-educated and not-so-humble opinion, but not "startling implications for the search for extra-terrestrial life" big. It'd be different if this were shown to have developed on it's own without input from "normal" biological life, but as it is it looks like just another extremophile to me.

The big deal is that it's not just tolerant of arsenic, it's that it actually integrates it into its bio-molecules. No other life form's ever been known to do so, and if this one exists, chances are there are others out there. The implication for extra-terrestrial life searches is that we can't just rely on looking only for the signatures of the 6 chemical elements that we previously thought all life had to be composed of, as this validates the possibility that completely different biochemistries are in fact viable.

Thanks for the reply. I got all that from the Ars writeup (which I agree with others was really good).

I guess I'm just non-plussed because, like a previous poster, I'd always assumed that exobiology would by necessity be radically different from from what we see on earth -- and besides, this is a bacteria that developed ON earth. Guess I was expecting something bigger...

I guess I'm just non-plussed because, like a previous poster, I'd always assumed that exobiology would by necessity be radically different from from what we see on earth -- and besides, this is a bacteria that developed ON earth. Guess I was expecting something bigger...

The problem is, so far that's all been purely the realm of sci-fi with absolutely not a single shred of proof that a non-carbon metabolic system was feasible/workable. This discovery not only validates that it's possible, it shows beyond doubt that such a system works. From a biochemistry standpoint that's huge.

I guess I'm just non-plussed because, like a previous poster, I'd always assumed that exobiology would by necessity be radically different from from what we see on earth -- and besides, this is a bacteria that developed ON earth. Guess I was expecting something bigger...

The problem is, so far that's all been purely the realm of sci-fi with absolutely not a single shred of proof that a non-carbon metabolic system was feasible/workable. This discovery not only validates that it's possible, it shows beyond doubt that such a system works. From a biochemistry standpoint that's huge.

NASA's press release suggested something more than "we've finally found some proof of something everybody has suspected for decades".

you need evidence of some difference before you can change a theory. Until this was found procedurally and defined scientifically, there was only *speculation* that life could form around other elements; all of the evidence to this point (meaning "life as we know it") had indicated that life used six elements for the chemical structures of DNA, RNA, proteins, and lipids.

There was, and there is still, no "theory" of what extraterrestrial life looks life. There can't be one, because we have no data, whatsoever, on this. For starters, such a theory would benefit from a real definition of "life", better that "we will recognize it if we see it".

So it is nice to know that terrestrial life can find alternate ways to use the chemistry it has access to, but the impact on the search of extraterrestrial life should be small if the researchers that do it have any sense of humility.

Yes, Ars, thank you, this is the only article that comes close to being accurate. When I read your article, I could get excited about the finding. When I read the untruths and hype on nearly every other tech site out there, I get too upset by the distortions simple stupidity to appreciate what has actually been found. And a big boo to NASA for misleading so many easily-lead and wide-eyed journalists.

I thought this was an exceptionally good article so I just wanted to say thanks.

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Very well written. I was able to grasp the implications of the science (extra-terrestrial life could exist in systems without the key six elements) with just my educational foundation consisting of high school bio and 100 level college chem.

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Ars science articles seem to hit that perfect balance between not dumbing it down so much that nothing is really explained and explaining the really technical parts enough that it makes sense. I dunno what it is, but every time I read one of these I get more and more excited as complex theories start unraveling for me in a way that makes perfect sense.

And then I also spit coffee on my keyboard at the comments, thanks drlava :/

Thanks for the reply. I got all that from the Ars writeup (which I agree with others was really good).

I guess I'm just non-plussed because, like a previous poster, I'd always assumed that exobiology would by necessity be radically different from from what we see on earth -- and besides, this is a bacteria that developed ON earth. Guess I was expecting something bigger...

Just because alien life may be using similar chemistry, doesn't mean that it won't be VERY different. Look no further than the variety in lifeforms here on Earth.

BTW, excellent article! This kind of article is why I keep coming back to Ars.

This is neat and all in my semi-educated and not-so-humble opinion, but not "startling implications for the search for extra-terrestrial life" big. It'd be different if this were shown to have developed on it's own without input from "normal" biological life, but as it is it looks like just another extremophile to me.

Am I missing something?

It IS an extremophile, but it's of a class that has not been encountered before. No organism has previously been discovered that uses a fourth period element as part of its genetic code. Conventional thinking in molecular biology would say it shouldn't be alive.

Yun Xie / Yun Xie / Yun Xie is a contributing science writer at Ars, where she covers the latest advancements in science and technology for Ars. She currently works in scientific communications, policy, and review.